This project focuses on basic and applied research on human retroviruses, HIV-1 and HTLV-I. It covers three broad areas: I) basic research studying the regulated expression of HIV-1; II) basic research on cellular transformation events as related to HTLV-I; and III) applied research towards developing small molecular inhibitors targeted against HIV-1. Some notable scientific advances from our research program in 2002-2003 include: 1) the finding that human RNA helicase DDX3 is a critical cofactor for HIV-1 post-transcriptional gene expression; 2) the characterization of poly arginine as an inexpensive inhibitor of HIV-1 envelope processing; 3) the demonstration of important regions in Tat necessary for eliciting an optimal immune response; 4) the identification of ubiquitination as a novel modification for Tax; 5) the elucidation of dual signals necessary for T-cell apoptosis; and 6) the discovery that the Tax protein has transcriptional activities after the formation of an initiation complex at the promoter.